rs3737454

Positions:

• chr11-77157232-C-A
• chr11-77157232-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000260.4(MYO7A):​c.736-47C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,491,962 control chromosomes in the GnomAD database, including 6,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1554 hom., cov: 33)
  • Exomes 𝑓: 0.071 (5028 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.29

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-77157232-C-A is Benign according to our data. Variant chr11-77157232-C-A is described in ClinVar as [Benign]. Clinvar id is 255667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77157232-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.736-47C>A		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.736-47C>A		intron_variant		1	NM_000260.4	ENSP00000386331
MYO7A	ENST00000409619.6	c.703-47C>A		intron_variant		1		ENSP00000386635
MYO7A	ENST00000458637.6	c.736-47C>A		intron_variant		1		ENSP00000392185	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17966 AN: 152136 Hom.: 1549 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0966 AC: 18633 AN: 192972 Hom.: 1402 AF XY: 0.0916 AC XY: 9462 AN XY: 103246

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0999

Gnomad EAS exome AF: 0.264

Gnomad SAS exome AF: 0.0929

Gnomad FIN exome AF: 0.0440

Gnomad NFE exome AF: 0.0511

Gnomad OTH exome AF: 0.0921

GnomAD4 exome AF: 0.0710 AC: 95129 AN: 1339708 Hom.: 5028 Cov.: 21 AF XY: 0.0708 AC XY: 47276 AN XY: 668034

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.0987

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.0920

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0537

Gnomad4 OTH exome AF: 0.0901

GnomAD4 genome AF: 0.118 AC: 18001 AN: 152254 Hom.: 1554 Cov.: 33 AF XY: 0.118 AC XY: 8807 AN XY: 74454

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0534

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0767 Hom.: 385

Bravo AF: 0.131

Asia WGS AF: 0.192 AC: 665 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Autosomal recessive nonsyndromic hearing loss 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Autosomal dominant nonsyndromic hearing loss 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Usher syndrome type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3737454; hg19: chr11-76868278; COSMIC: COSV68684915;